The SEK-1 p38 MAP Kinase Pathway Modulates Gq Signaling in Caenorhabditis elegans

摘要

Gq is a heterotrimeric G protein that is widely expressed in neurons and regulates neuronal activity. To identify pathways regulating neuronal Gq signaling, we performed a forward genetic screen in Caenorhabditis elegans for suppressors of activated Gq. One of the suppressors is an allele of , which encodes a mitogen-activated protein kinase kinase (MAPKK) in the p38 MAPK pathway. Here, we show that mutants have a slow locomotion rate and that acts in acetylcholine neurons to modulate both locomotion rate and Gq signaling. Furthermore, we find that acts in mature neurons to modulate locomotion. Using genetic and behavioral approaches, we demonstrate that other components of the p38 MAPK pathway also play a positive role in modulating locomotion and Gq signaling. Finally, we find that mutants in the p38 MAPK pathway partially suppress an activated mutant of the sodium leak channel, /NALCN, a downstream target of Gq signaling. Our results suggest that the p38 pathway may modulate the output of Gq signaling through (unc-77).